1,721,058 research outputs found
Combining Ipilimumab and Bevacizumab in Glioblastoma is Really Safe and Effective?
No full textThe proposed data regarding
the safety and efficacy of the combined use of ipilimumab
plus bevacizumab in glioblastoma patients should be very
cautiously considered
Oncology and a time of crisis. Science, complexity, ethic values, and incertitude. An argumentative essay
No full textWho faces a neoplastic disease is more bewildered than in the past, in spite of the improvement of the possibility of cure and priority attributed to this subject by the health institutions and medicine, compared to few decades ago. Nevertheless, disorientation is increasing due to many factors, also beyond those of the scientific and welfare context of cancer and is related to the general background of crisis. The landscape of crisis involves the changes occurring in both epistemic and contextual values, and methodology of science at large, as well as those particular of the medical field, including oncology. The perceived ltoss of reliability of universal laws and the limits of general theories, in favor of the conception that elementary events concurr to outcomes, makes the scientific appraisal more probabilistic than deterministic. This framework of “complexity” is characterized by non-linearity in the causal links, opacity of the investigated subject, and emergence of the phenomena we observe and analyze. In oncological medicine, the present deterministic “gold standard” of the random comparative trials, grounding the so-called evidence-based medicine (EBM), and the guidelines for clinical management - although being the most reliable resource - are critically considered. In fact, new “systems biology” approaches, based on big data analysis and advanced statistical methods, may bridge the gaps between the biological/pre-clinical and clinical investi-gations, hopefully allowing “precision” or “personalized medicine”. Artificial Intelligence is consi-dered an indispensable tool to this regard. However, also this approach couldn’t effectively work without a sound, general theory on cancer, presently not at hand. Moreover, all of the above contexts suffer of the pressure of industry, interested in the economic impacts. On the other hand, the costs of cancer management, increasing at a higher rate compared to care results, motivate the health authorities to take physicians out of the personal professional and trust relationship with the patients. In this situation, oncologists have mainly to cooperate – often in a subordinate position - with bureaucratic professionals for the implement-tation of pre-established guidelines. As a consequence, patients are institutionalized and deprived of the reassuring presence of an entrusted doctor, thus experiencing enhancement of distress and solitude feelings. This connects with crisis in the social domain, defined as a strength that conquers autonomy without a manifest theory of itself, thus without a project, but with an impact capacity producing high perceivable effects. This existential landscape characterizes the present time as “the age of incertitude”. Complexity and uncertainty thus exist also in society. The social pact between individual and state (relinquishing of a part of freedoms by the former in exchange for security by the latter) is compromised, and the indeterminate nature of the crisis obscures any solution. The statements on the right to health are perceived as abstract formulations, generating mistrust in institutions and further distress. From the physicians’ point of view, this must not imply loss of responsibility, but even more so imposes a great ethic commitment. They must operate as best as they can, despite being aware that the desired effects could be vanished by context. This is a further subject to consider in the relationship between medicine and health institutions: the former must preserve its own statutory purposes of prevention and care of diseases in the best possible way, even if the inherent epistemic complexity and the contextual background makes this task more problematic than in the past. Indeed, medicine should cooperate with health institutions, developing the necessary attitudes given the present social background, but not in a subordinate role, as far as its intellectual and operative domains are concerned. Another factor of crisis must be considered, that is, communication. A diagnosis of cancer, an ominous event, induce to look for any glimmer of hope and entrusts false believes or pseudo-scientific results, because these appear easier to comprehend and promise clear-cut good results, compared to the scientific argumentations, hard to understand and expressed in terms of probability. The present cultural background of society is affected by the lack of humanistic education, that is, what grounds critical thinking. Biomedical researchers and physicians, sometimes suffering of the same deficiency, regrettably have also other faults, that is, defects in intellectual honesty such as egocentrism and self-reference that can generate mistrust in science on the long run. After examining these items in the light of the available data and authoritative sources of the related literature, we reached the conclusion that a “new alliance” can be promoted between oncological science and society, based on “the humanism of science”. Improving
intellectual honesty by the biomedical community, as well as critical thinking also in society is mandatory. This can be obtained with suitable educational programs in high school and university. Cultural empowerment, and a realistic approach to the epistemic and ethics issues on cancer may mitigate the related individual and social discomfort and - hypothetically - improve clinical outcomes through the increased patients’ compliance to therapy and prevention programs
Emerging Targets For Prostate Adenocarcinoma Therapy: How Molecular Biology May Drive Towards a More Tailored Approach
No full textProstate adenocarcinoma is the most diagnosed male cancer in the Western world and the second leading cause of cancer-related mortality. Albeit most of the patients with prostate adenocarcinoma are currently treated by surgery and/or radiation therapy, more than 30-40% of affected subjects will eventually progress and develop advanced disease. To date, management decisions depend on the clinical stage of the patient and the histological diagnosis which unfortunately often lack to predict the real prognosis. Current therapies have shown to be insufficient, mainly in the metastatic disease. For clear-cut diagnosis and follow-up, we promptly need molecular markers also useful in predicting patient's outcome. Advances in cancer genomics have led to a plethora of biomarkers, which must now to be rigorously validated in the clinical setting. Recent insights on prostate adenocarcinoma biology which unveiled some of the biological mechanisms leading to this tumour, have managed in devising novel strategies for therapy. Immunotherapeutic agents, selective adrenal inhibitors, anti-angiogenic molecules, newly engineered androgen receptor inhibitors, compounds targeting the bone microenvironment are demonstrated to limit cancer growth by blocking specific signaling pathways. Such strategies can be complemented to existing therapeutic paradigm in improving beneficial outcome. Moreover, other emerging pharmacological compounds have shown encouraging results and several clinical trials are ongoing. In this review summarize the developing targeted therapies for prostate adenocarcinoma and discuss their potential benefit mainly in the castration-resistant forms
Primary neuroendocrine (Merkel cell) carcinoma of the eyelid in a young woman - Report of a Case
No full textIs there a potential role for EGFR expression to lead margin reduction in glioblastoma?
No full textWe started to investigate a potential role for EGFR protein expression in predicting the modality of treatment failure in glioblastoma after Stupp protocol, in terms of both time-to-progression (TTP) and pattern of
recurrence (PR) [central/in-field (C/I-F) vs. marginal/distant (M/D)]. EGFR expression is statistically correlated with
TTP (log-rank test: p = 0.003) and PR (Fisher’s exact test: p = 0.01). Our results seem to suggest that EGFR expression
might have a potential role for target contouring of RT volumes in GB patients that deserves further prospective investigations
Cyclin D1 Co-localizes with Beclin-1 in Glioblastoma Recurrences: A Clue to a Therapy-induced, Autophagy-mediated Degradative Mechanism?
No full textBackground: Glioblastoma (GB) recurrences are rarely removed, therefore, tissue modifications induced by radiotherapy, and temozolomide chemotherapy are scarcely known. Nuclear cyclin D1 is associated with GB progression and resistance to therapy. We previously found that the expression of autophagic protein beclin-1 is a major determinant of prognosis in GB. Patients and Methods: In 31 patients with primary GB and their recurrences, we investigated the protein expression of cyclin D1 and beclin-1, before and after radiotherapy-temozolomide therapy by immunohistochemistry. Results: Most (20/31) primary GBs were negative for nuclear cyclin D1, and highly expressed beclin-1. In their recurrences, cytoplasmic cyclin D1 positivity was observable, which co-localized with beclin-1. Eleven primary GBs instead exhibited low beclin-1 expression and were positive for nuclear cyclin D1; three of their recurrences exhibited an increase of beclin-1, which co-localized with cyclin D1 in the cytoplasm. Conclusion: Our results suggest therapy-induced degradation of cyclin D1 via autophagy
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